A natural experiment study: Low-profile double plating versus single plating techniques in midshaft clavicle fractures—Study protocol

Background Single plate osteosynthesis is commonly employed when performing surgical stabilization of midshaft clavicle fractures. In recent years, a smaller structural low-profile double plating technique has been described as a possible solution for the high removal rates associated with single plating. A previous meta-analysis has demonstrated that low-profile double plating attains the same healing rates as single plating without a higher chance of fracture-related infections. This meta-analysis, however, was based on relatively small studies. Therefore, a multicentre prospective natural experiment was designed using natural variation in treatment regimens and geographical location of the trauma as treatment allocation mechanism to compare both treatments on a larger scale. This manuscript describes its protocol. Material & methods Patients (≥16 years) with primary midshaft clavicle fractures that are eligible for operative treatment will be included. Treatment allocation will be determined by the geographical location of the accident and local hospital providing treatment. In two centres, single plating is the treatment of choice for these patients. In two others, low-profile double plating has become the standard treatment. For the low-profile double plating group, one superiorly positioned VariAx 2.0mm and one anterior VariAx 2.4mm or 2.7mm plate will be used. For the single plating group, the standard locally available implant will be used. A total of 336 patients will be included. The primary outcome of interest is re-intervention. Secondary outcomes include complications, operative time, length of incision, functional scores (DASH, EQ-5D-DL, VAS-Pain/Satisfaction) and cost-effectiveness. Discussion This study will determine whether low-profile double plating has significant clinical and cost-effective benefits over single plating techniques in midshaft clavicle fractures. The study will also give insight in the performance of a natural experiment study design for orthopedic trauma research. Trial registration This study has been registered on ClincialTrials.gov, identifier NCT 05579873.


Background
Exposed to the exterior environment due to a lack of surrounding muscles or subcutaneous tissue, the clavicle is prone to traumatic injury.Clavicle fractures account for 5 to 6% of all fractures, of which 69 to 81% occur in the midshaft.[1,2] Surgical stabilization using a single plate, positioned either anteriorly or superiorly, is the most common surgical technique when patients/surgeons decide on operative treatment.[3] The major disadvantage of plate fixation, however, is implant irritation.As a result, up to 64% of patients undergo re-interventional surgery for implant removal.[4] In recent years a low-profile double plating technique with smaller plates has been described as a possible solution to reduce the high rates of implant irritation.[5] Biomechanically, low-profile double plating is expected to be at least as stable as single plating.[6] A recently published meta-analysis showed that low-profile double plating for midshaft clavicle fractures is a safe procedure attaining the same high union rates seen in patients treated with single plating.[7] Additionally, double plating appears to have a lower overall complication and reintervention rate, mainly due to the lower incidence of implant-related complaints.Low-profile dual plating, however, is a relatively new technique and should be further explored to test whether our findings can be confirmed.
Although randomized controlled trials (RCTs) are considered the gold standard for testing the effectiveness of such new interventions, the artificial conditions that are usually imposed on surgical practice frequently limit the feasibility and the generalizability of its results.A natural experiment (NE) design offers a possible solution.NEs are observational studies in which patients are exposed to either the experimental or the control condition, and treatment allocation is determined by factors outside the control of the investigators (e.g., geographical location).[8] Although not the same, the process governing treatment allocation arguably resembles that of randomization, since treatment allocation is expected to be (to a large extent) independent of patients' characteristics and their prognosis.This protocol encompasses a prospective NE comparing low-profile double plating to single plating in midshaft clavicle fractures.The primary endpoint is the overall re-intervention rate, with a specific interest in implant removal due to irritation.Secondary endpoints include all complications, healing, the general quality of life, functional results, and cost-effectiveness.

Aim
To compare single plating to low-profile double plating in midshaft clavicle fractures with regard to re-intervention, complications, healing, quality of life, functional results, and cost-effectiveness.

Study design
This study will be a multicenter prospective cohort study between four Swiss centers with comparable patient case-mix.At which hospital/surgeon trauma patients are presented after an accident depends on the geographical location of the accident.We hypothesize that different Swiss centers treat a similar caseload of trauma patients with clavicle fracture and that the patient case-mix is similar across the different centers.If eligible, the treating physician or local investigator will explain to each participant the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits, and any discomfort it may entail.Each participant will be informed that participation in the study is voluntary, that he or she may withdraw from the study at any time, and that withdrawal of consent will not affect his or her subsequent medical assistance and treatment.The participant will be informed that their pseudonymized medical records may be examined by authorized researchers other than their treating physician.

Data management
Data will be stored in pseudonymized form in an encrypted online database by the local investigators, which can access their respective individual patient data.Full access to the database is granted to the study coordinator.

Low-profile double plating group
Low-profile double plating consists of one Stryker VariAx 2.0mm plate positioned on the superior aspect of the clavicle and a second Stryker VariAx 2.4mm or 2.7mm on the anterior side.Use of this implant will be according to the manufacturer's indication of use.

Single plating group
The choice of implant used for single plating is left at the discretion of the treating surgeon and the availability of implants in participating centers.Possible implants consist of 2.7 and 3.5mm plates placed on the superior or anterior side.

Standardization of care
Preoperative care will consist of general anesthesia and routine antibiotic prophylaxis.Incision and cutaneous nerve sparing are left at the treating surgeon's discretion and will be mentioned in the operation report.In case of a multi-fragmentary fracture pattern, bridge plating will be performed.In case of a simple fracture, a neutralization plate (with or without lag screws) or a compression plate will be used.Closure of deltopectoral fascia with absorbable braided sutures and skin with absorbable or nonabsorbable monofilament sutures will be performed for all patients.Operations will either be performed or directly supervised by a specialized trauma surgeon.Aftercare comprises a sling for comfort for 1-2 weeks, no weight bearing for six weeks, and outpatient clinic visits, including AP and axial clavicle X-rays at six weeks, three months, and one year after surgery in both treatment groups.

Study outcomes
The primary outcome of this study is the number of re-interventions after two years of follow-up.
Secondary outcomes include the number of re-interventions at one year of follow-up, all complications such as fracture-related infection [10], (a)symptomatic non-union, numbness below the scar, and self-reported implant irritations, disability of the shoulder and arm (DASH) score, EuroQol (EQ)-5D score, and the visual analogue scale (VAS) score for pain and patient satisfaction at 3, 12, and 24 months follow-up.A complete overview of the primary and secondary outcomes can be found in Table 1.

Secondary Objective
Re-intervention rate (including implant removal) after 1-year follow-up.
Version 5, 01.04.2023:A natural experiment study: Low-profile double plating versus single plating techniques in midshaft clavicle fractures -Study protocol 0.05, power = 0.8) approximately 152 patients per treatment group are needed.To compensate for a potential 5% loss to follow-up, a total of 336 patients are required.

Statistical analysis.
The statistical package IBM SPSS Statistics for Windows, version 28.0, will be used for analysis.
Depending on the normality distribution, baseline characteristics will be described as means and standard deviations or median and interquartile range for continuous variables.Categorical variables will be reported in counts and percentages.Differences between treatment groups will be analyzed with an independent samples student's T-test or Mann-Whitney-U test (depending on distribution).Categorical variables will be analyzed using the Chi-square test.
The primary outcome will be analyzed using logistic regression with revision surgery as the dependent and treatment as the independent variable.The relative risk (RR) will be calculated with a 95% confidence interval (95% CI).Multivariable logistics regression analysis will also be performed to account for potential known confounders including age and fracture type.
Missing data (caused by incomplete hospital documentation or loss-to-follow-up) will be addressed using multiple imputation techniques.

Discussion
Previously, a meta-analysis on single vs low-profile double plating demonstrated that low-profile double plating attains the same healing rates as single plating without a higher chance of fracturerelated infections.[7] This study however, was based on studies with relatively small sample sizes.
The present NE study will provide the required evidence to confirm or revoke the aforementioned conclusions based on a more extensive study population.Additionally, this study will form the basis for a more prominent use of the NE design in the surgical research.Due to its design, this study has a high feasibility with minimal burden to the participants, since the received care is that of daily clinical practice.Not only will the study help us understand if low-profile double plating has significant clinical and cost-effective benefits over single plating techniques in midshaft clavicle fractures, but it also provides new insights into how the NE design functions in a research field where it has rarely been used before.

Ethics approval and consent to participate
This study was ethically approved by the Northwestern and central Swiss ethics commission.The identifier number is 2022-00574

Publication
Publications based on the results obtained shall not be made before the first multicentre publication or presentation, which shall be coordinated by the principal investigator unless otherwise agreed in writing.The manuscript shall be published in a peer-reviewed journal.

Consent for publication
Not applicable

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Figure 1
Figure 1 Schedule of enrolment, interventions, and assessments

Figure 2
Figure 2 In/Exclusion criteria

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